الفهرس 
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Abstract
Most of the new chemical entities (NCE) under development are intended to be
used as solid dosage forms originating an effective and reproducible in vivo plasma
concentration after their oral administration. Unfortunately, an increasing number of
new chemical entities emerging from drug discovery and reaching drug development
are poorly or very poorly water soluble. Therefore, an urgent need has always existed
to improve the dissolution, solubility and consequently the oral bioavailability of
these poorly water-soluble drugs.
Flutamide is the only nonsteroidal antiandrogen presently recommended for
monotherapy of prostate cancer. The low bioavailability of FLT after oral
formulations may be due to poor wettability, low aqueous solubility, poor
permeability and rapid first pass hepatic extraction .The inadequate absorption of FLT
through the gastrointestinal tract (GIT) may not be due to its inability to permeate the
intestinal epithelium, but to its low concentration at the absorption surface.
Formulations that produce higher concentrations of FLT in solution at the absorption
site may overcome the solubility-mediated bioavailability deficiencies.
Peptide drugs are attracting an increasing interest with a better understanding of
their role in physiopathology, as with the progress in biotechnology and biochemical
synthesis. However, the use of peptides and proteins in medicine has been limited by
low oral bioavailability which results from their poor stability to proteolytic and
hydrolytic degradation, low permeability across barriers, and short biologic half-life.
Most therapeutic peptides are still being administered by the parenteral route because
of their insufficient absorption from the gastrointestinal tract.
The objective of this thesis is to improve the drug targeting and enhance the oral
bioavailability of Flutamide and Albumin which are of low bioavailability and require
innovative formulation approaches to reach a sufficiently high bioavailability after
their oral administration.
This thesis is divided into two parts:
Part One: Development of Controlled Release Formulations of Flutamide.
Part one is subdivided into two chapters:
Chapter One: Preparation and Evaluation of Immediate-Release Flutamide
Formulae using the Lyophilization Monophase Solution
Technique.
Chapter Two: Preparation and Evaluation of Controlled-Release Flutamide-
Chitosan Microparticles.
Part Two: Preparation and Evaluation of Chitosan Nanoparticles as Oral
Controlled Release Drug Delivery System for Proteins and Peptide
Drugs.
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Part One
Development of Controlled Release Formulations of Flutamide
Chapter One
Preparation and Evaluation of Immediate-Release Flutamide Formulae using
the Lyophilization Monophase Solution Technique
The aim of this chapter is to formulate FLT lyophilized dispersions in order to
improve the drug aqueous solubility, dissolution rate and to facilitate faster onset of